Prospective-retrospective analysis of the incidence of thyroid tumor gene mutations in Bethesda III– VI cytological findings and their implementation in the clinical practice of surgical de-escalation and/ or individualized treatment

Czech version

Authors: J. Astl ^1-3 ; B. Peková Bulanová ⁴ ; J. Rotnágl ^1,2 ; R. Holý ^1,2 ; B. Bendlová ⁴ ; O. Vorobiov ^1,2 ; J. Soukup ⁵ ; J. Hložek ^1,2
Authors‘ workplace: Klinika otorinolaryngologie a maxilofaciální chirurgie 3. LF UK a ÚVN Praha ¹; 3. lékařská fakulta, Univerzita Karlova, Praha ²; Katedra otorinolaryngologie, IPVZ, Praha ³; Oddělení molekulární endokrinologie, Endokrinologický ústav, Praha ⁴; Oddělení patologie, ÚVN Praha ⁵
Published in: Otorinolaryngol Foniatr, 73, 2024, No. 3, pp. 125-133.
Category: Original Article
doi: https://doi.org/10.48095/ccorl20241125

Overview

Introduction: The incidence of thyroid tumours is increasing worldwide. The most common malignant tumours of the thyroid gland include well-differentiated carcinomas (WDTC), especially papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC). Medullary thyroid carcinoma (MTC) is less commonly diagnosed. Genetic changes determine the aggressive behavior of tumours and increase the metastatic potential of thyroid tumours. The aim of the study is to determine the incidence of point gene mutations and gene fusions in patients with Bethesda III–VI cytology as a possible predictor of indication of the extent of surgical procedures on the thyroid gland. Materials and methods: The study was prospective-retrospective and included patients operated on at the Department of Otorhinolaryngology and Maxillofacial Surgery of the 3^rd Faculty of Medicine, Charles University and the Military University Hospital from July 1, 2019 to July 1, 2022, i.e. a period of 36 months. In the detection of the BRAF V600E gene, the allele of specific Real-Time PCR (LC480, Roche), the TERT gene mutation by direct sequencing (CEQ 8000, Beckman Coulter) was used, samples were analyzed by PCR (MiSeq, Illumina), and the Thyro-ID panel (4base) was used to detect another 12 genes. In addition, 23 fusion genes were tested, including ALK, BRAF, GLIS3, NTRK1, NTRK3, PPARG, and RET gene using Real-Time PCR, and MTC test for mutations in the RET gene and RAS. Results: The study included 273 patients with preoperative cytology Bethesda III–VI. The study was based on 21 (7.7%) men and 256 (93.77%) women. In the group, 103 (37.72%) cancers were histologically confirmed and 170 (62.27%) were found to have a benign tumour. Bethesda III were benign histologies with 118 (63.78%) that were verified, and 67 patients (36.21%) were diagnosed with any type of carcinoma. In Bethesda IV, there were 50 (70.42%) confirmed benign histologies and 21 patients (29.58%) had malignant tumours. BRAF V600E point mutation was detected in 63.85% of papillary thyroid carcinoma and only once in a benign tumour, and one NIFTP case was confirmed. Papillary carcinoma was presented in 83 (76.14%) patients, follicular carcinoma and its variants was in 14 (12.84%) patients, and medullary carcinoma was detected in 6 (5.5%) cases in the group. Conclusions: BRAF V600E point mutation was detected in 63.85% of well differentiated thyroid carcinomas and in other diagnoses, any mutation detected was rare.

Keywords:

de-escalation – Fusion genes – thyroidectomy – BRAF V600E – thyroid carcinoma – point mutations of genes – NLR paresis

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ORCID autorů

J. Astl 0000-0002-8022-0200,

B. Peková Bulanová 0000-0002-8571-164X,

J. Rotnágl 0000-0003-2692-0342,

R. Holý 0000-0001-8073-3658,

B. Bendlová 0000-0001-7008-8675,

O. Vorobiov 0000-0001-5314-1075,

J. Soukup 0000-0001-7169-4386,

J. Hložek 0000-0002-3584-9747.

Přijato k recenzi: 10. 4. 2024

Přijato k tisku: 8. 7. 2024

as. MUDr. Jiří Hložek